Many neurological diseases such as dementia, including Alzheimer's disease, stroke, depression, Parkinson's disease and motor neuron disease are associated with a reduction in the number of neurons. The decline in number of neurons may be rapid, as in the case of stroke, or slower, as in the case of Alzheimer's disease.
After heart disease and cancer, stroke is the third leading cause of death in western industrialized countries and the major cause of severe, long-term disability in adults with 56% of people following a stroke suffering from a severe or profound disability. There are over 20 million stroke survivors worldwide. Over 40,000 stroke events occur in Australia each year—one every 12 minutes, one every 45 seconds in the USA. This ailment represents an economic burden estimated to be $45 billion a year in the US alone and is expected to rise significantly. A significant factor contributing to this trend is the increased susceptibility to stroke among the elderly.
Alzheimer's disease is the most common dementia occurring in the elderly, affecting about 10% of people above 65 years and 40% above 80 years. Alzheimer's is predicted to afflict up to 16 million people by the middle of this century unless a cure or prevention is found in the United States alone. 50-75% of dementia is estimated to be caused by Alzheimer's disease. The prevalence of Alzheimer's disease is slightly higher in women than in men, but almost twice as many women live with dementia because of their longer life expectancy.
Alzheimer's disease is a progressive neurodegenerative disease characterized by memory loss and general cognitive and behavioural decline. Alzheimer's disease is commonly associated with a non-cognitive symptomatology including depression. Histologically, Alzheimer's diseased is defined by the presence in post-mortem human brain specimens of amyloid neuritic plaques, the formation of neurofibrillary tangles and degeneration of the cholinergic neurons.
Parkinson's disease is associated with the destruction of neurons, but the damage is restricted to the dopamine-producing cells in the substantia nigra (part of the basal ganglia). The most common symptoms of Parkinson's disease are tremor, rigidity and difficulty initiating movement. In the US alone, some one million patients are affected and 50,000 new patients are added annually.
Motor Neuron Disease is the name given to a group of diseases in which nerve cells that control the muscles degenerate and die. It is rarely diagnosed in people less than 30 years of age. In Australia, there are around 400 new cases of motor neuron disease each year. There is no effective method of treatment and the disease is generally fatal within 1-5 years of diagnosis. More than one person dies of Motor Neuron Disease each day in Australia.
There are several regions in the brain where stem cells are known to exist, including the sub-ventricular zone and the olfactory bulb. It is thought that the stem cells in these areas are already working at maximum capacity to generate new neurons for general “self-maintenance”. Additionally, neurogenesis occurs in the subgranular cell layer of the adult hippocampal dentate gyrus and has important consequences in learning and memory (Shors et al., 2001). A number of environmental and behavioural stimuli have been shown to enhance hippocampal neurogenesis and this is thought to be mediated through synaptic activity (van Praag et al. 1999; Brown et al., 2003; Santarelli et al., 2003; McEwen, 1994). Since large numbers of hippocampal cells are generated throughout the lifetime of an animal it is predicted that a stem cell is most likely responsible. Surprisingly, however, the precursors identified so far that generate these cells have limited self-renewal (Bull and Bartlett 2005; Seaberg and van der Kooy et al., 2002). Despite the limited capacity for self-renewal of the cells so far identified, it has been shown that excitation caused by applying depolarizing levels of extracellular potassium mimics the effects of stably increased activity, as would occur in an active neural network, and leads to an increase in neuron production from hippocampal adult neural progenitor cells (Deisseroth et al., 2004).